Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

• Published in: PloS one Vol. 10; no. 9; p. e0138843
• Main Authors: Johnston, Sara C, Lin, Kenny L, Twenhafel, Nancy A, Raymond, Jo Lynne W, Shamblin, Joshua D, Wollen, Suzanne E, Wlazlowski, Carly B, Wilkinson, Eric R, Botto, Miriam A, Goff, Arthur J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.09.2015; Public Library of Science (PLoS)
• Subjects: Aerosols; Aerosols - administration & dosage; Analysis; Animal models; Animal research models; Animals; Development and progression; Ebola virus; Epidemics; Exposure; Fatalities; Fever; Filoviridae; Genetic aspects; Health aspects; Hemorrhage; Hemorrhagic disease; Histopathology; Infections; Infectious diseases; Injections, Intramuscular; Kaplan-Meier Estimate; Macaca fascicularis; Marburg virus disease; Marburg Virus Disease - blood; Marburg Virus Disease - virology; Marburgvirus - physiology; Medical research; Pathogenesis; Pathology; Permeability; RNA, Viral - blood; Studies; Temperature; Viral diseases; Virology; Viruses; United States; Angola; United States > US; Maryland; Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138843

Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.